Because of the complexity of the human body and the complication of various diseases, disease management continues to be the most challenging and active area in medicine. Herein disclosed are a system and an approach to apply shear stress for disease treatment. Some examples of diseases are brain diseases, including meningitis, epilepsy, neurological trypanosomiasis, progressive multifocal leukoencephalopathy. Further examples of diseases are cancers, including malignant neoplasms, benign neoplasms, metastases, and hematological malignancies. Due to the vastness pertaining to this field, brain diseases and cancers are taken as examples to illustrate some important principles and their applications in treating diseases.
Brain diseases remain major clinical challenges despite the fast development in medicine. One of the primary reasons that results in such challenges lies in the structure of the blood-brain barrier (BBB). The blood-brain barrier is composed of high density cells restricting passage of substances from the bloodstream much more than endothelial cells in capillaries elsewhere in the body. It is a membrane in the central nervous system (CNS) that allows the passage of substances essential to metabolic functions (e.g. oxygen) but restricts that of many chemical substances and microscopic objects (e.g. bacteria) between the bloodstream and the neural tissue. This “barrier” derives its function from the selectivity of the tight junctions between endothelial cells in CNS vessels that restricts the passage of solutes. As a result, it is very difficult to deliver drugs to the brain to manage various brain diseases (e.g., meningitis, epilepsy, neurological trypanosomiasis, progressive multifocal leukoencephalopathy); even though suitable drugs are available or will become available. Therefore, it is of vital importance to find methods to deliver drugs to the brain in their nano-size or sub-nano-size forms.
Cancer is one of the greatest threats to human health. According to the 2008 cancer statistics report by the American Cancer Society, cancer caused nearly 560,000 deaths in the United States in 2005, occupying 22.8% of all deaths and ranking as the second killer after heart diseases (26.6% of all deaths). The battle against the threat of cancer continues in clinical, industrial, and research institutions. The understanding of the cause, nature, and progression of various cancer types has led to many methods for cancer treatment, such as surgical excision, chemotherapy, radiotherapy, immunotherapy, and gene therapy.
It is discovered that tumorous tissues exhibit higher activities than normal tissues to recruit blood vessels in order to sustain the over-proliferation of the tumor cells. Furthermore, tumors are not only highly vascularized but also leaky in nature. This has provided the basis for many drug delivery strategies, especially in the case of passive targeting.
Metastases, on the other hand, are the main cause of deaths for cancer patients. Tumor cells shed from primary tumors, enter lymphatic and blood vessels, circulate in the bloodstream, and settle down to grow in other normal tissues in the body. The new tumors are called secondary tumors or metastatic tumors, wherein the cells are like those in the primary tumors. Most primary tumors can metastasize, though in varying degrees (e.g., glioma and basal cell carcinoma rarely metastasize). It is understood that tumorous cells are weaker compared to normal cells. As a result, the change in the environment (e.g., pH, shear stress) can destroy the cancer cells while sparing the healthy/normal cells. Therefore, it is possible to treat the blood (ex-situ) in a shear device so as to destroy the cancer cells that are travelling in the bloodstream while preserving the health of the normal cells, after which the treated blood is re-circulated into the patient via infusion. This method has great value in treating hematological malignancies, such as leukemia, lymphoma, multiple myeloma.
It has also been shown that cellular uptake of molecules is enhanced by exposing them to high shear stress for short durations. This phenomenon renders the potential of loading cells with therapeutic agents as a mechanism for drug delivery and the potential of enhancing drug efficacy while applying shear stress to cancer cells.